Department of Medical Pathomorphology, Medical University of Bialystok, Collegium Pathologicum, Waszyngtona St. 13, 15-269 Bialystok, Poland.
In Vivo. 2010 Jan-Feb;24(1):101-7.
The aim of this study was the assessment of expression and location of CX32 and CX43 in colorectal adenomas and carcinomas as well as analysis of expression of these proteins in association with clinical and pathological features of tumors and evaluation of mutual relationships between CX32 and CX43.
The study included 151 primary colorectal carcinoma and 71 colorectal adenomas. The control group comprised 30 colon samples. Connexins were detected with immunohistochemistry.
There was a lack of membranous distribution of connexins or a shift from moderately membranous immunoreactivity to predominantly cytoplasmic accumulation of CX32 and CX43 in studied colon tumors. Mentioned alterations were found in adenomas and augmented in cancer. Expression of Cx32 was significantly associated with grading of colorectal cancer, implicating a role of intracellular CX32 in regulation of tumor growth and differentiation. A strong correlation was present between CX32 and CX43 in node-positive cases and absent from node-negative ones.
To our knowledge, our study is the first illustration for a gradual loss of functional gap junctions within progression of colorectal neoplasia. An intracellular location of connexins, the site of their common and the most frequent detection within cancer cells in our study may be of significance. Independently of its role in functional gap-junctions, cytoplasmic CX32 could be involved in cancer differentiation, resulting in a higher rate of CX32 positive moderately differentiated tumors (G3) than poorly differentiated CX32-positive ones (G3).
本研究的目的是评估 CX32 和 CX43 在结直肠腺瘤和癌中的表达和定位，分析这些蛋白的表达与肿瘤的临床和病理特征的关系，并评估 CX32 和 CX43 之间的相互关系。
本研究包括 151 例原发性结直肠癌和 71 例结直肠腺瘤。对照组包括 30 例结肠样本。使用免疫组织化学法检测连接蛋白。
在研究的结肠肿瘤中，CX32 和 CX43 缺乏膜分布或从中度膜免疫反应转移到主要细胞质积累。在腺瘤中发现了这些改变，并在癌症中增加了。Cx32 的表达与结直肠癌的分级显著相关，表明细胞内 CX32 在调节肿瘤生长和分化中起作用。在有淋巴结转移的病例中，CX32 和 CX43 之间存在很强的相关性，而在无淋巴结转移的病例中则不存在。
据我们所知，我们的研究首次说明了在结直肠肿瘤发生过程中功能性缝隙连接的逐渐丧失。在我们的研究中，连接蛋白的细胞内定位，即它们在癌细胞中最常见的共同检测部位，可能具有重要意义。细胞质 CX32 可能参与了癌症的分化，导致 CX32 阳性中度分化肿瘤（G3）的比例高于 CX32 阳性低分化肿瘤（G3），而与功能性缝隙连接无关。
